Hepatitis B virus (HBV) infection, while preventable by routine vaccination, has already led to chronic HBV infection (CHB) in about 240 million people worldwide. Although antiviral drugs are available, these must be taken daily for life and are unaffordable for most of world's CHB population. Consequently, a therapeutic vaccine is needed that would stimulate sufficient immunity to control CHB. Because CD8+ T cells are both necessary and sufficient for clearing HBV from the liver, a therapeutic vaccine must elicit extremely strong anti-HBV CD8+ T cell responses. Such a vaccine must be strong enough to counter the PD-1/PD-L1 and CD4+ regulatory T cells (Tregs) that suppress effective anti-HBV CD8+ T cells in CHB. Mouse studies have shown that stimulation the CD40 receptor on dendritic cells can generate anti-HBV CD8+ T cells that are strong enough to overcome these suppressive mechanisms and lead to long- term HBV control. Consequently, this project aims to use a powerful form of soluble multi-trimer CD40 ligand (CD40L) in conjunction with the HBV Core antigen (HBcAg). The result is a fusion protein comprised of the multimerization scaffold (SPD) with Core antigen and CD40L (SPD- Core-CD40L). This is referred to as a Multi-Trimer Antigen Adjuvant Vaccine or MagaVax. The Aims are to make the construct in an adenoviral vector, test its effectiveness at eliciting anti- HBV CD8+ T cells in mice in vivo, and show that i can activate human dendritic cells to present Core antigen to HBV-specific human CD8+ T cells in vitro. When these studies are complete, a MagaVax/HBV vaccine will be ready for further testing and development as treatment for CHB.